Systemic Therapy for Hereditary Breast Cancers.

Approximately 5% to 10% of all breast cancers are hereditary; many of which are caused by pathogenic variants in genes required for homologous recombination, including BRCA1 and BRCA2. Here we discuss systemic treatment for such breast cancers, including approved chemotherapeutic approaches and also targeted treatment approaches using poly-(ADP ribose) polymerase inhibitors. We also discuss experimental approaches to treating hereditary breast cancer, including new small molecule DNA repair inhibitors and also immunomodulatory agents. Finally, we discuss how drug resistance emerges in patients with hereditary breast cancer, how this might be delayed or prevented, and how biomarker-adapted treatment is molding the future management of hereditary breast cancer.

Early age of first sex and health risk in an urban adolescent population.

BACKGROUND: Early sex is associated with high-risk behaviors and outcomes, including sexual risk behaviors, forced sex, physical dating violence, and becoming pregnant or impregnating someone. METHODS: Using 2005 and 2007 data from the New York City Youth Risk Behavior Survey (N = 17,220), this study examined the prevalence of early sex among public high school students; associations between early sex and other sexual risk factors and violence indicators; and whether associations varied across 4 racial/ethnic groups. Bivariate and multiple logistic regression models estimated the relationship between sexual risk and violence outcomes and "early sex," defined as first having sexual intercourse before age 14. Separate models with an interaction term for early sex by race/ethnicity were also estimated. RESULTS: More than one third of students who ever had sex reported having early sex. Adolescents reporting early sex were significantly more likely than those reporting later sex to engage in most sexual risk behaviors and to experience violence. The magnitude of association varied significantly by race/ethnicity for sexual risk behaviors. CONCLUSIONS: The high prevalence of early sex, coupled with its associated high-risk behaviors and outcomes, underscores the necessity of implementing evidence-based interventions that have been found to positively impact these behaviors beginning in middle school.

Stimulation of methane generation from nonproductive coal by addition of nutrients or a microbial consortium.

Biogenic formation of methane from coal is of great interest as an underexploited source of clean energy. The goal of some coal bed producers is to extend coal bed methane productivity and to utilize hydrocarbon wastes such as coal slurry to generate new methane. However, the process and factors controlling the process, and thus ways to stimulate it, are poorly understood. Subbituminous coal from a nonproductive well in south Texas was stimulated to produce methane in microcosms when the native population was supplemented with nutrients (biostimulation) or when nutrients and a consortium of bacteria and methanogens enriched from wetland sediment were added (bioaugmentation). The native population enriched by nutrient addition included Pseudomonas spp., Veillonellaceae, and Methanosarcina barkeri. The bioaugmented microcosm generated methane more rapidly and to a higher concentration than the biostimulated microcosm. Dissolved organics, including long-chain fatty acids, single-ring aromatics, and long-chain alkanes accumulated in the first 39 days of the bioaugmented microcosm and were then degraded, accompanied by generation of methane. The bioaugmented microcosm was dominated by Geobacter sp., and most of the methane generation was associated with growth of Methanosaeta concilii. The ability of the bioaugmentation culture to produce methane from coal intermediates was confirmed in incubations of culture with representative organic compounds. This study indicates that methane production could be stimulated at the nonproductive field site and that low microbial biomass may be limiting in situ methane generation. In addition, the microcosm study suggests that the pathway for generating methane from coal involves complex microbial partnerships.